1. Field of the Invention
The present invention relates to lipid particles and an application thereof, and suitably relates to lipid particles which is useful for delivering nucleic acids into cells, and a nucleic acid delivery carrier.
2. Description of the Related Art
Nucleic acid medicines are disclosed as next-generation pharmaceutical products since an action mechanism thereof with respect to a disease is obvious and there are few adverse reactions. For example, nucleic acid medicines in which RNA interference (RNAi) is used can cause decomposition of mRNA of a target gene existing in a cell and can inhibit expression of the target gene. As a result, it is possible to reduce or treat diseases and symptoms caused by abnormal expression of a specific gene or a gene group. Nucleic acids, for example, siRNA, are used in such nucleic acid medicines in which RNA interference is used. However, it is necessary to deliver nucleic acids into cells in order to exhibit a function with these nucleic acids.
In general, a carrier (vector) is used in methods for effectively delivering nucleic acids into cells. Examples of the carrier (vector) include a viral carrier and a non-viral carrier. Since viral carrier has highly unclear points in terms of pathogenicity, immunogenicity, and safety in cytotoxicity, it is desired to use an non-viral carrier from the viewpoint of the safety.
A cationic carrier which can hold nucleic acids through an electrostatic interaction is used as the non-viral carrier since nucleic acids are anionic. A cationic liposome in which cationic lipids having a specific structure are used or a composite in which a cationic polymer is used is generally known as an example of the cationic carrier.
As an example of the cationic liposome, a liposome formed of cationic lipids, 1,2-dioleoyl-3-sn-phosphatidylethanolamine (DOPE), and polyethylene glycol lipids is disclosed in Gene Therapy, Vol. 6, p. 271, 1999. In addition, lipid particles formed of a first cationic lipid, a second cationic lipid, a neutral lipid, and a polyethylene glycol lipid are disclosed in WO2012-00104A in addition to lipid particles containing 50 mol % to 85 mol % cationic lipids.
Furthermore, a composite in which a cationic polymer is used is also known (Journal of Controlled Release 114 (2006) pp. 100 to 109).
In addition, as examples of means for further improving the cationic carrier in which cationic lipids are used, an amphoteric liposome in which cationic lipids and anionic lipids are combined is disclosed in JP2011-21026A, and an amphoteric liposome formed of amphoteric amphiphilic lipids is disclosed in JP2005-517739A.